Allelic Variation of Human Serotonin Transporter Gene Expression

Heils, Armin; Teufel, Andreas; Petri, Susanne; Stöber, Gerald; Riederer, Peter; Bengel, Dietmar; Lesch, Klaus‐Peter

doi:10.1046/j.1471-4159.1996.66062621.x

Cited by 2,074 publications

(1,410 citation statements)

References 11 publications

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“…65 Several polymorphisms in the SLC6A4 gene have been described, including a variable number tandem repeat in exon 2, 66 a restriction fragment-length polymorphism in the 3 0 untranslated region, 67 and a variable number tandem repeat polymorphism in the 5 0 promotor region, termed the 5-HTT gene-linked polymorphic region (5-HTTLPR). 68 The 5-HTTLPR has two common alleles: a 'long' (l) allele with 16 imperfect repeats of an approximately 22-base-pair element and a 'short' (s) allele with 14 repeats.…”

Section: -Httlpr Long and Short Allelesmentioning

confidence: 99%

“…68,[70][71][72][73] However, the translation of in vitro findings into in vivo functioning does not appear straightforward. Human neuroimaging studies of 5-HTT availability [74][75][76][77][78][79] and post-mortem studies of 5-HTT bindings and rRNA expression [80][81][82] have not detected any consistent effect of 5-HTTLPR.…”

Section: The Functionality Of 5-httlprmentioning

confidence: 99%

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The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis

2007

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Section: -Httlpr Long and Short Allelesmentioning

confidence: 99%

Section: The Functionality Of 5-httlprmentioning

confidence: 99%

The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis

2007

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“…The most common assessed variants are a deletion/ insertion polymorphism in the transcriptional control region of the SLC6A4 gene with functional effects (5HTTLPR) [227][228][229] and a variable number of tandem repeat in intron 2 (STin2). Several studies have found an association of the short alleles of 5HTTLPR with AD, 217,[230][231][232][233] fewer studies of the long alleles.…”

Section: Chromosome 17mentioning

confidence: 99%

The genetics of autistic disorders and its clinical relevance: a review of the literature

2006

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Twin and family studies in autistic disorders (AD) have elucidated a high heritability of the narrow and broad phenotype of AD. In this review on the genetics of AD, we will initially delineate the phenotype of AD and discuss aspects of differential diagnosis, which are particularly relevant with regard to the genetics of autism. Cytogenetic and molecular genetic studies will be presented in detail, and the possibly involved aetiopathological pathways will be described. Implications of the different genetic findings for genetic counselling will be mentioned.

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“…17 The 5-HTTLPR was genotyped using PCR amplification. 18 To determine if there were any differences in nongenotype confounds between the genotype groups, one-way ANOVA and w 2 tests were used.…”

Section: Subjectsmentioning

confidence: 99%

A regulatory variant of the human tryptophan hydroxylase-2 gene biases amygdala reactivity

et al. 2005

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Recent studies have indicated that a newly identified second isoform of the tryptophan hydroxylase gene (TPH2) is preferentially involved in the rate-limiting synthesis of neuronal serotonin. Genetic variation in the human TPH2 gene (hTPH2) has been associated with altered in vitro enzyme activity as well as increased risk for mood disorders. Here, we provide the first in vivo evidence that a relatively frequent regulatory variant (G(À844)T) of hTPH2 biases the reactivity of the amygdala, a neural structure critical in the generation and regulation of emotional behaviors. Keywords: TPH2; amygdala; serotonin; fMRI Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of serotonin (5-HT), a key modulator of mood and affect. Thus, the identification of genetic variation contributing to functional changes in TPH enzymatic activity is of great interest in determining the biological pathways underpinning individual differences in emotional behaviors and risk for psychiatric disorders, including depression, anxiety, and suicidality. Recent molecular and cellular studies have revealed the existence of a second TPH isoform, tryptophan hydroxylase-2 (TPH2), exclusively expressed in the murine brain. 1 Functional assays demonstrate that TPH2-and not the original isoform, referred to now as TPH1-is responsible for regulating TPH expression and 5-HT synthesis in the murine central nervous system. 2 In contrast, both TPH1 and TPH2 are expressed in the human brain 3 and genetic variation in both isoforms have been associated with alterations in mood and 5-HT function. 4,5 Furthermore, a relatively rare single nucleotide polymorphism in human TPH2 (hTPH2) associated with depression has been shown to alter TPH enzymatic efficiency in vitro. 6 However, the functional consequence of genetic variation in hTPH2 on the neural circuitry of mood and emotional behaviors is unknown.In the current study, we used functional magnetic resonance imaging (fMRI) to examine the effects of a single nucleotide polymorphism (G(À844)T) in the upstream regulatory region of hTPH2 on the reactivity of the amygdala, a central structure in the mediation of behavioral and physiologic arousal associated with emotional behaviors. Although the molecular and cellular effects of the G(À844)T polymorphism are unknown, we focused on this regulatory variant for several reasons. First, unlike other hTPH2 variants with demonstrated impact on enzymatic activity, 6 the G(À844)T has a relatively high minor allele frequency (T allele ¼ 38%) and thus, has the potential to contribute more broadly to brain function and risk for mood disorders. Second, this variant is located within 1 kb (844 bp upstream) of the transcription initiation site of hTPH2 and is likely a constituent of the proximal promoter of the gene. Regulatory variants in general often impact gene expression 7 and several specific promoter polymorphisms in other 5-HT subsystem genes have demonstrated effects on brain function and emotional behaviors. [8][9][10]

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Allelic Variation of Human Serotonin Transporter Gene Expression

Cited by 2,074 publications

References 11 publications

The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis

The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis

The genetics of autistic disorders and its clinical relevance: a review of the literature

A regulatory variant of the human tryptophan hydroxylase-2 gene biases amygdala reactivity

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